The in-situ delivery of therapeutic agents within the body of a patient is common in the practice of modern medicine. In-situ delivery of therapeutic agents is often implemented using medical devices that may be temporarily or permanently placed at a target site within the body. These medical devices can be maintained, as required, at their target sites for short or prolonged periods of time, in order to deliver therapeutic agents to the target site.
In some cases however, delivery of the biologically active material to the body tissue immediately after insertion or implantation of the medical device may not be needed or desired. For instance, if a stent is used to prevent the occurrence of restenosis after balloon angioplasty, it may be more desirable to wait until restenosis occurs or begins to occur in a body lumen that has been stented with a drug-coated stent before the drug is released. Therefore, there is a need for insertable or implantable medical devices that can provide delayed and/or controlled delivery of biologically active materials when such materials are required by the patient after implantation of the medical device. The in-situ delivery of therapeutic agents in a controlled manner often involves the use of a nanoporous material through which the therapeutic agents are transported.
Nanoporous materials have the potential to revolutionize drug delivery. For example, iMEDD, Inc. has created silicon membranes with parallel channels ranging from 4 to 50 nm. Diffusion rates of various solutes through such membranes have been measured and conform to zero-order kinetics in some instances (i.e., release is constant with time). This is in contrast with typical situations in which drug diffusion rates decay with time, because the concentration gradient, and thus the driving force for diffusion, is also decaying with time. One explanation for zero order behavior is that, by making the diameter of the nanopores only slightly larger than that of the drug, the nanopores act as bottlenecks, forcing the drugs to proceed in a substantially single-file fashion through the membrane. iMedd claims that the membranes can be engineered to control rates of diffusion by adjusting channel width in relation to the size of solutes. When the proper balance is struck, zero-order diffusion kinetics is possible.
Current techniques for the in-situ delivery of therapeutic agents in a controlled manner often involve the use of a polymeric nanoporous coating on the insertable or implanatable medical device to contain the agents and control their release rate. The polymeric coating, however, can sometimes cause an inflammatory response in the tissue with which it comes in contact. For instance, when a Drug Eluting Stent (DES) is implanted in a vessel, the inflammatory response can cause a reduction in the diameter of the vessel lumen within the stent. The inflammatory response can lead to late in stent thrombosis.